Open lumen air filtration for liquid lines

ABSTRACT

Devices and systems for capturing and removing accumulated gas bubbles in a liquid-carrying line wherein the device is an expanded double-layered chamber designed and adapted to be integrally placed within the flow pathway of a liquid-carrying line. The device allows insertion of tubes and wires through the device while in use without occlusion of the fluid flow path and without interruption of the bubble-removing function. The efficiency of the air venting and bubble-removing process is not dependent on the fluid flow rate under stable flow conditions, and the device works to remove air bubbles under a range of orientations.

BACKGROUND

The problem of gas bubbles in a fluid-carrying line is very along-standing and well-known one. This problem is of considerableimportance in various applications in which a liquid is conductedthrough a conduit, and is particularly troublesome in medicalapplications. Currently, there is no adequate solution to this problem.Gasses may enter the fluid-filled line in a gaseous state as bubbleswithin the fluid, or it may be present in a dissolved state within thefluid, and come out of solution under the influence of changingpressures or temperatures. The gas molecules so produced coaless underentropic and hydrophobic influences to form discrete bubbles within thefluid. These bubbles can interrupt and/or block the flow of a fluid.Such blockage or interruption can be problematic for many sorts ofmedical and industrial equipment where an uninterrupted flow isdesirable. Many analytical and diagnostic devices, especially those thatemploy the flow of very small volumes of a liquid, are very sensitive tosuch interruptions in flow. When small volumes are involved or at lowReynolds numbers where viscous forces are dominant, the effects ofsurface tension and other forces at a liquid-gas phase boundary becomepronounced and can inhibit flow. These problems are particularly acutein microfluidic applications.

In a medical context, when intubation is required, for example with acatheter, drip or other conduit designed to introduce (or remove) liquidfrom the body of a subject, such blockage or interruption can haveadverse consequences and can even be fatal, such as when an air bubbleenters the blood stream. Air embolism (for example venous, pulmonary orcerebral) is a well-known and potentially fatal complication that canoccur in patients with central venous catheters (CVCs) as a consequenceof the entry of air into the vasculature upon removal of the catheter,and many articles exist describing various methods used to preventformation of an embolus. Less risk is associated with the use ofperipherally inserted central catheters (PICC), but the risk ofembolization is still a serious one. Venous air embolism (VAE) occursmostly during surgical procedures in which the operative site is 5 cm orhigher above the right atrium or gas is forced under pressure into abody cavity and is often cited as a complication of neurosurgery, but itcan also occur during procedures involving the head and neck,laparoscopic procedures, vaginal delivery and caesarean section, andspinal instrumentation procedures.

The current approach to this problem is to manually prime the fluidline, by flushing fluid through it, just prior to use to ensure removalof any air bubbles present. The operator such as the doctor, nurse orparamedic, visually checks the visually translucent line to determine ofany bubbles are present, often tapping the line to dislodge bubbles, andthen flushes the line with excess fluid to make sure that any bubblespresent are flushed out and that no bubbles are visually present.

Commercial valves and air vents may be placed within the line to preventgas build-up and so that bubbles that do form may be removed from theline. Valves are usually manually employed by raising the line at thesite of the valve so that the bubbles rise to the valve and then openingthe valve to flush out any bubbles present.

Commercially available gas/air venting devices are available,particularly for use with medical applications, which are able to ventgas/air from liquid lines without need for manual vents or valves.Examples include IV air filter devices, such as those supplied by PallCorp and Qosina Corp, and cardiopulmonary bypass surgery blood airfilters, such as the Dynamic Bubble Trap by DeWitt Group Int'l and ECBlood Filter® by Pall Corp. These devices use hydrophobic micro-porousmembranes to vent gas captured within IV tubes. To allow for sufficientexposure of air pockets/particles with the microporous membranes, thefilter divides entering flow into micro-channels. By decelerating theadvection rate of the air pockets and increasing the surfacearea-to-volume ratio, these microchannels allow for air bubbles to havegreater contact with the membranes for filtration to occur. However theuse of use of these air venting filters is limited primarily by theirsplit channel design, which does not allow for compatibility withcatheters, sheaths and endovascular interventional devices that largelyrequire simultaneous passage of liquid and catheters/wires. Otherlimitations of these current technologies include an inherent dependenceon infusion rate (flow rate) to control filtration efficacy, i.e. athigher flow rates, gases pass through the micro-channels faster andcarry less contact with hydrophobic vent membranes. Also, the currenttechnologies suffer from undesirable mechanical resistance to flow dueto the split channel design. The design of the current inventionaddresses these three limitations by offering full compatibility withguidewires, catheters and other endovascular devices concurrent withliquid infusion. Since the device separates air/gas from infusing liquidsolution, air filtration efficacy is decoupled from infusion rate. Inaddition, the single, continuous lumen imposes minimal mechanicalresistance on flow and infusion capacity.

The current solutions, for example manual flushing of lines of openablevalves positioned within a line, present other inherent problems. Onecurrent deficit is that the process of recognizing the presence or gasbubbles in the line is visual and requires active checking. Anotherdeficit is that the process of removal of gas bubbles is manual andsubject to human error. A further deficit is that such methods cannotremove air bubbles that may arise subsequent to checking and insertionof the line, such as when gas comes out of solution due to the effectsof increasing temperature and or decreasing pressure. Another deficit ofthe current solution is that the efficiency of removal of air bubbles isat least partially dependent upon having a reasonably low fluid flowrate through the line. The faster the fluid flows in the line, the morelikely it is that any bubble trapped in the line will pass by any valveand will not therefore be removed. Many infusing solutions (such asradio-opaque contrast solutions) are infused at a relatively fast rate,and thus, the current air venting mechanisms are not a viable solution.None of the current solutions contains an air bubble capture system orbubble trap that removes gas bubbles from the flowing liquidirrespective of the rate of liquid flow through the tube. Additionally,the current solutions do not adequately address the removal of airbubbles arising from the connection or re-connection of fluid lines andinsertion of catheters/wires into, for example, a guide/introducersheath.

There is a long-felt need for air venting devices that trap gas bubbles,that remove gasses from a line irrespective of the rate of fluid flowand that function while allowing insertion of wires, tubes and othersolid devices during liquid flow.

Additionally there is a need for such air-venting devices that vent gasbubbles in many medical, analytical, diagnostic and industrialapplications, such as hot water heating systems, cardiopulmonary pumps,contrast solution power injectors, endoscopes, chromatographyapparatuses, and microfluidic devices e.g., the Fluidigm devices such asthose described in U.S. Pat. No. 7,118,910 “Microfluidic Device AndMethods Of Using Same”; U.S. Pat. No. 6,752,922 “MicrofluidicChromatography”; and U.S. Pat. No. 6,951,632 “Microfluidic Devices ForIntroducing And Dispensing Fluids From Microfluidic Systems”; each ofwhich is hereby fully incorporated by reference for all purposes to theextent allowed by law.

A number of references describe technology and devices relevant to thepresent invention and show some previous solutions to the presenttechnological problems. But none of these references disclose or suggestthe present invention. These references include the following.

U.S. Pat. No. 4,689,047 “Air Venting Winged Catheter Unit”. Thisdisclosure describes a winged catheter unit enabling the user tointroduce intravenous fluids while permitting the technician to controlair venting at the onset of the I.V. introduction and during change ofI.V. bottles without removal of the catheter.

U.S. Pat. No. 4,227,527 “Sterile Air Vent” describes a sterile air ventwhich permits the passage of gas but is substantially impervious tomicroorganisms. The vent is suitable as a tip protector for the tip endsof medical fluid administration sets or the like and filtering isprovided by a solid micro-porous plug.

U.S. Pat. No. 5,334,153 “Catheter Purge Apparatus and Method of Use”describes balloon catheters with an air purging feature.

U.S. Pat. No. 4,324,239 “Safety Valve for Preventing Air Embolism andHemorrhage” describes a safety valve with an integrated piston.

U.S. Pat. No. 5,533,512 “Method and Apparatus for Detection of VenousAir Emboli” describes a respiratory gas monitoring system to detectemboli.

U.S. Pat. No. 3,982,534 “Intravenous Administration System” describes anintravenous administration system with three separate units fordelivering fluids.

U.S. Pat. No. 5,108,367 “Pressure Responsive Multiple Input InfusionSystem” describes an infusion system for administering multiple fluidsat individually programmable rates and volumes. The system has a primingmode that detects and removes air bubbles in the fluid line.

U.S. Pat. No. 3,844,283 “Apparatus for Aseptically Dispensing a MeasuredVolume of Liquid Apparatus” discloses a device for dispensing volumes ofliquid with a conventional cut-off valve to eliminate the need forintroducing contaminating environmental air.

US20020022848A1 “Method and Apparatus for Minimizing the Risk of AirEmbolism when Performing a Procedure in a Patient's Thoracic Cavity”describes an apparatus for minimizing the risk of air embolism includesan instrument delivery device having a gas outlet for delivering gasinto a patient's thoracic cavity.

The present invention provides a simple and effective solution to thelong-standing and well-known problem of gas bubbles in fluid-carryinglines. This problem is of considerable importance in various manyapplications, particularly in medical applications.

DEFINITIONS

In the present disclosure, the following words are used is the followingways.

“Line” is used to mean any elongated tube made of any material that maybe opaque or translucent and that in various embodiments is made of aninert of biocompatible material such as silicone plastics or similarmaterials.

“Liquid” means any liquid including biological fluids, saline etc.

“Bubble” refers to any quantity of a gas in a liquid, whether visible ornot.

“Venting” is a verb that refers to the removal of a gas from an enclosedarea, such as from a liquid-carrying tube.

“Air filter” means a device designed to capture and/or remove a gas froma liquid flowing through a line. The word “trap” or “air trap” may alsobe used to describe such a device.

Gauge (or gage) pressure is defined as the pressure within the filter(at the inner surface of the filter membrane) minus the pressure at theouter surface of the filter casing.

The phrase “integrally placed within a line”, when referring to an airfilter, simply means that the air filter is placed within the lateralaxis of a line such that a liquid flowing through the line will flowthrough the air filter. The air filter may be removable from the lineand may be removably coupled into the line, using, for example,leur-lock or snap-fit joints gasket joints or any suitable locking jointthat provides a liquid-tight seal under normal working conditions. Tosay that a filter is placed “in-line” with a conduit or tube or flowpathway or fluid-carrying line is the same as saying that the filter is“integrally placed within a line”, as above.

To say that the inner and outer wall is “partially in contact” with theouter wall means that the two walls are in less than complete contactwith each other. The walls may be in contact to any degree from 1 to99.9% of their surface areas, such as 10%, 25%, 50%, 75%, 90% or 95% incontact with each other.

The word “diameter” when used with respect to pores in a membrane,refers to the longest distance between the sides of the pores, so thatin the case of a diamond shaped pore, the diameter is the longestdistance between any two points on the perimeter of the pore.

BRIEF DESCRIPTION OF THE INVENTION

The present invention encompasses devices, systems, methods and kits forremoving accumulated gas bubbles in a liquid-carrying line. In variousspecific embodiments, the invention comprises the following.

A filter for capturing and removing accumulated gas bubbles present in aliquid-carrying line, the filter adapted for integration into theliquid-carrying line, the filter having an expanded chamber having aninlet end and an outlet end, wherein the maximum diameter of theexpanded chamber is greater than the diameter of the portion ofliquid-carrying line into which it is adapted to be integrated, andwherein the expanded chamber includes an inner wall and an outer wallconstructed so as to form two concentric chambers having a liquid flowpath through the axis of the inner chamber, and wherein the inner wallis, under conditions of use, permeable to gasses but impermeable toliquids.

The expanded chamber can be spherical or ovoid. The shape of theexpanded chamber is asymmetrical, having a generally narrower diameterclose to the inlet end and a generally broader diameter close to theoutlet end.

The design of the present invention allows gas capture and venting whileconcurrently using instruments passing through the conduit, such ascatheters, sheaths and endovascular interventional devices.

The design of the present invention allows for inserted cylindricalobjects (e.g. wires, tubes) to be self-guided towards the outlet.

The axisymmetric design provides air filtering under all orientations,with optimal filtration performance under all flat rotationalorientations. The device provides >80% filtration performance under lowReynolds numbers (less than ˜10).

The design of the present invention means that filtration efficacy isgenerally not dependent on infusion rate (flow rate) under stable flowconditions. Our tests have shown stability in flow models simulatingflows of up to 1200 cc/hr in a 8 Fr. compatible device (or Reynoldsnumbers of less than 4800). Unstable flow conditions occur when theReynolds has reached the point where the fluid boundary layers are nolonger separated by a core fluid stream and all fluid within the deviceis in a mixing regime.

The design of the present invention does not use a split channel design,but uses a single channel design, thereby reducing overall resistance toflow when compared with the split channel design. The single, continuouslumen imposes minimal mechanical resistance on flow and infusioncapacity. In a split channel configuration, there is a split in a liquidline, in other words, a bifurcation or division of a central or inletflow into two/more liquid channels. The split channel design filter hasmultiple (i.e. more than one) parallel-arranged paths for liquid flow.Therefore, in a split channel design filter liquid can take more thanone fluid path from the device's inlet to its outlet. In the case of amedical filter employing this split channel design, the “split channels”are lined with a hydrophobic or other air-filtering membrane. The “splitchannels” are intended to increase the filtration surface area-to-airvolume ratio to enhance filtration efficacy.

In contrast, in a non-split channel design filter, entering fluid canonly take a single path from the inlet to the outlet of the device.

In various embodiments, the inner wall comprises a microporous membrane.In certain embodiments this microporous membrane is hydrophobic. Themicroporous membrane has pores that may have, for example, an averagediameter of between 0.1-50 microns under zero hoop-stress. Themicroporous hydrophobic membrane may be comprised of a material selectedfrom the group consisting of polytetrafluoroethylene, vinylidenefluoride (VDF), tetrafluoroethylene, vinylidene fluoride,hexafluoropropylene, carbon black, elemental sulfur, a glass composite,nylon, polyethersulfone and acrylic copolymer. In addition, to create amicroporous membrane with hydrophobic properties, a material withminimal or void of hydrophobic properties, such as polyvinylidenedifluoride (PVDF) or cellulose, may be used as a base substrate bycoating it with a hydrophobic material (such as those presented above).In some embodiments, the microporous membrane has pores that are diamondshaped. The pores are designed to open or become more open when themembrane is stretched.

In various embodiments, the outer wall is made of a perforated materialselected, for example, from the group of plastics consisting of acrylic,ABS [Acrylonitrile Butadiene Styrene], Methyl Methacrylate AcrylonitrileButadiene Styrene, nitrile, polycarbonate, polyethylene, nylon, PVC[polyvinyl chloride], acetyl, silicone, polysulfone, polystyrene,polyisoprene, copolyester, polyethersulfone, polyvinylidene fluoride,polyurethane, ethylene vinyl acetate copolymer and polypropylene. Thisouter wall may also be made of a metallic material, such as stainlesssteel, copper, nickel-coated steel, brass, aluminum, silver, iron ornickel-titanium. The perforated material may be made of a translucentmaterial, may be gas permeable or impermeable, and may have valvesintegrated within it. The outer wall may be flexible or rigid.

In use, when the internal pressure inside the inner wall increases, theinner wall expands to fill the volume in which it resides, contactingand pushing outwards upon the outer wall.

The filter acts passively and automatically to trap and air bubblespresent in the liquid flowing through the line and is designed so thatthe microporous membrane becomes increasingly gas permeable withincreasing liquid pressures within the liquid flow path.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic drawing showing a longitudinal section of the airfilter with zero internal gauge pressure. In the coordinate displays,“R” and “Z” represent radial and axial, respectively.

FIG. 2 is a schematic drawing that shows a longitudinal section of theair filter with positive internal gauge pressure.

FIG. 3 is a schematic drawing of a magnified view of the microporoushydrophobic membrane under zero membrane hoop stress or zero fluid gaugepressure.

FIG. 4 is a schematic drawing of a magnified view of the microporoushydrophobic membrane under compressive membrane hoop stress or negativefluid gauge pressure.

FIG. 5 is a schematic of a magnified view of the microporous hydrophobicmembrane under tensile membrane hoop stress or positive fluid gaugepressure.

FIG. 6 is a drawing showing a longitudinal section of the joint assemblyin detail.

FIG. 7 is a schematic diagram depicting position stability of air bubbleat the top of the filter lumen with imposed blunt fluid and buoyancyforces to allow for venting of air through the hydrophobic membrane andouter casing.

FIG. 8 is a schematic diagram depicting the opening of a check-valvewhen pressure inside the filter is positive relative to its exterior.

FIG. 9 is a schematic diagram depicting the closing of a check-valvewhen pressure inside filter is zero or negative relative to itsexterior.

FIG. 10 is a graph of volumetric flow rate through porous 0.2 micrometerpore PTFE membrane

FIG. 11 is a graph of volumetric flow rate through porous 1.0 micrometerpore PTFE membrane

FIG. 12: is a graph of water intrusion pressures through PTFE membraneFIG. 13: is a table showing results of tests of prototype filter

DETAILED DESCRIPTION OF THE INVENTION

The invention provides devices, systems, methods and kits for removingaccumulated gas bubbles in a liquid-carrying line.

Embodiments of the present invention encompass a device that filters,captures and vents gas bubbles from a liquid-carrying line. The filterof the invention maintains an open lumen to allow for insertion of tubesand wires (e.g. catheters and guidewires for endovascular interventionrelated applications) through the device concurrent with liquid infusionthrough the device.

Important advantages of the present design include the following: (1)The design of the present invention allows gas capture and venting whileconcurrently using instruments passing through the conduit, such ascatheters, sheaths and endovascular interventional devices. (2) Thedesign of the present invention means that filtration efficacy is notdependent on infusion rate (flow rate). (3) The design of the presentinvention does not use a split channel design, but uses a single channeldesign, thereby reducing overall resistance to flow when compared withthe split channel design. The single, continuous lumen imposes minimalmechanical resistance on flow and infusion capacity.

In a general embodiment, the air filter comprises an expanded chamberdesigned and adapted to be integrally placed within a line, the expandedchamber having an inlet end and an outlet end. The diameter of theexpanded chamber is greater than the diameter of the line into which itis integrated.

The shape of the expanded chamber, in certain embodiments, can beapproximately spherical or ovoid. The expanded chamber can be of anasymmetrical shape that is narrower close to the inlet end and broaderclose to the outlet end. In other embodiments, the expanded chamber canbe of other shapes such as rectangular, polyhedral or irregular.

In certain embodiments, the ratios of dimensions of the filter are as,for: [inlet flow diameter:max luminal diameter:total filter length],vary as follows: [1:5.5:28], [1:9.5:30 ], [1:9.5:54] (The filterdimension ratios may be any value between the three sets providedabove). These values represent dimensionless units which are normalizedover the inlet flow diameter and may be apply to any size structureproportionally within the ranges provided.

In certain embodiments, the expanded chamber is made of a plasticmaterial that is rigid, and in other embodiments, can be made of anon-rigid, flexible and/or elastic material.

In some embodiments, the expanded chamber is translucent, allowing anoperator to see within the chamber, to visually determine whetherbubbles and/of liquids are present.

In a preferred embodiment, the expanded chamber is a double-walledchamber having a first, inner wall and a second, outer wall. Essentiallythe structure resembles an inner bag that is contiguous with the fluidflow path through the line, and an outer bag that surrounds the innerbag. In preferred embodiments, the first, inner wall comprises amicroporous membrane. A microporous membrane is a thin-walled structurewith a plurality of pores extending through the thickness of thematerial. A hydrophobic microporous membrane is a microporous membranecarrying resistance and strong aversion to wetting and penetration ofwater-based liquids/solutions.

In certain embodiments, the second, outer wall (also called outercasing) comprises a perforated, liquid-porous or gas-porous material,and in other embodiments the outer wall is not perforated and isimpermeable to fluids but may have valves integrated within it.

The first and second walls may be in contact with each other orpartially in contact with each other over some percentage of theirareas, or may have an air gap between them and be substantiallyseparated from one another. In certain embodiments, the microporoushydrophobic membrane of the inner wall is substantially in contact withperforated outer casing.

In use, when the internal pressure inside the first (inner) wallincreases, the first wall expands to fill the volume in which itresides, contacting and pushing outwards upon the second (outer) wall.See FIG. 2 that shows the air filter with positive internal gaugepressure.

The air filter is positioned within the lateral axis of a line such thata liquid flowing through the line will flow through the air filter.

In use, the air filter will be positioned in an approximately horizontalorientation with respect to the ground. The greater the expansion of thefilter luminal profile relative to the inlet/outlet diameter, the higherthe capacity to bring the filter to near a vertical position withoutrisking migration of bubbles downstream. Buoyancy is only one kinematicdriver of gas bubbles towards the membrane for ventilation. Two othersare decelerating flow within the lumen and the high pressure gradientacross the membrane observed by gas pockets (because of the membrane'shydrophobic properties this gradient is not “felt” by water). Underslower flow rates and large expanded shape, the majority of gas pocketswould be vented by the filter if placed in a true vertical orientation.Due to these three drivers, the filter achieves optimal filtration whenplaced in a true horizontal position (perpendicular to the earth'sgravitational axis). In a vertical position, buoyancy is working againstthe intended mechanism of the filter, however, the pressure gradientacross the membrane and decelerating flow will allow for less thanoptimal filtration to take place. Under lower Reynolds conditions, wherethe pressure gradient and decelerating flow significantly overcome theantagonizing buoyancy forces, reasonable filtration efficacy may beachieved. In use, gasses and bubbles are trapped by and collect withinthe expanded chamber and do not simply pass through it as would happenin a vertical orientation. To say that the air filter is positioned inan approximately horizontal orientation with respect to the ground meansthat the long axis of the air filter forms an angle of not more thanabout 45 degrees to the horizontal.

In certain preferred embodiments the air filter has an axi-symmetricdesign, such that at any point along the axis of the filter a crosssection would be a perfect circle. The implication of the axi-symmetricdesign is that the filter has equivalent performance under allrotational orientations. The air filter has a diffuser-shaped entranceand nozzle-shaped exit, where the two shapes are merged in a parabolicconfiguration. The goal of the filter profile is to decelerate flowwithout creating unstable flow separation zones. Upon entering the inletof the filter, the flow decelerates due to an expansion of the filterlumen (expansion may be of a straight/linear or curved shape). At themid-section of the filter (marked by termination of the diffuser and thesection with the largest inner diameter), the flow reaches its lowestvelocity within the filter. Towards the distal end of the filter, thefilter must restore flow to its original velocity, which is achieved bya nozzle shaped distal end (this nozzle also may be of linear/straightor curved shape. However, the transitions between the diffuser, expandedsection of the filter and nozzle must be smooth to ensure optimal flowstability within the filter. Instability would cause mixing of gas andwater within the filter and not allow for gas to maintain a steadyposition for ventilation. Thus the filter provides a parabolictransition between the diffuser and nozzle sections of the filter.However, more generally this transitional shape must be smooth (i.e. nonotches, grooves, edges, etc). Another purpose for the nozzle end of thefilter is to provide a means for a cylindrical-shaped object (e.g. wire,tube) which is inserted through the filter to self-guide itself towardsthe outlet.

In a preferred embodiment, the filter is composed of at least twodifferent materials (see FIG. 1). The inner wall consists of amicroporous hydrophobic membrane which serves as an obstruction toliquid but not air. The material of this microporous membrane may, forexample, be PTFE (polytetrafluoroethylene), a glass composite, nylon,polyethersulfone or acrylic copolymer or other similar materials.

In preferred embodiments, the pore sizes of the microporous hydrophobicmembrane are sufficiently small under zero hoop-stress so that when theinternal fluid pressure in the line falls below that of ambient pressure(the pressure on the outside of the filter device), the small-sizedpores present high resistance to air flow at zero and negative gagepressures. Under positive pressures within the filter, the membrane willstretch and cause the pores to open. The size of the outer casing actsas a maximum limit for the stretching and opening of the membrane pores,which by design, prevents over-stretching of the pores and an otherwiseunacceptable water breakthrough pressure capacity. Under negative andzero gauge pressures within the filter, the pores remain “shut” (similarto a valve mechanism), thus preventing air/gas from entering the filterlumen.

The average pore sizes of the microporous hydrophobic membrane may rangefrom between 0.2-20 microns in diameter under zero hoop-stress (i.e.stress in the circumferential direction). The average pore diameterunder zero hoop-stress may, for example, range from 0.01 to 200 microns;from 0.05 to 150 microns; from 0.1 to 100 microns; from 0.1 to 50microns; from 0.2 to 50 microns; from 0.2 to 20 microns; from 0.5 to 10microns; from 0.05 to 20 microns; or from 0.5 to 10 microns.

The pores of the microporous hydrophobic membrane will be furthercollapsed by compressive hoop stresses. Compressive hoop stresses occurunder negative gauge pressures within the filter. Closing of the poresunder negative pressure prevents gas from intruding into the filterlumen. For example, when the filter is applied to a catheter device, ifblood is drawn through the catheter (e.g. via a syringe), negativepressure will develop within the filter, closing the pores to act likevalves to inhibit gas flow into the filter.

The pore size and pore density of the membrane is such to allow for asufficient rate of passage of air across the filter membrane underanticipated pressure gradient ranges (where pore diameter ranges from0.2-20 microns and pore density is between 10-50%). Sufficiency of rateof air flow across the membrane is based on desired volumetric gasfiltration rate. In selecting the optimal membrane, considerations mayinclude anticipated internal pressures within the filter and the maximumflow/infusion rate through the filter. The achievable gas volumetricflow rate through the filter is governed by pore density (relativeamount of open area for gas to penetrate membrane) and internal filterpressure (i.e. pressure gradient to drive flow through membrane). Thewater break-through pressure is dictated by the membrane's pore size(i.e. pressure at which the water's pressure gradient across themembrane exceeds the hydrophobic interfacial tension). Thus, thismembrane's pore size is selected such that under the range ofanticipated filter pressures, the membrane does not exceed itsbreakthrough pressure. Thus the filter of choice may be the one whichhas the opportunity to vent a 100% gaseous infusion through the filter.]Any pressure above zero psi may allow gas to flow out of the filter.Pressures at or below 0 psig will not allow passage of gas in/out of thefilter.

The thickness of the microporous hydrophobic membrane is relativelysmall, ranging from between about 0.0127 mm-1.27 mm. A thinner membraneis more easily ‘stretchable’ than a thick membrane. Under a given gaugepressure, a thinner membrane will stretch more due to higher hoop stressthan a thicker membrane. Higher gauge pressure within the filter iscaused by higher infusion rate through the filter. In medicalapplications, if a catheter or sheath is placed within blood, the filteris by default subjected to blood pressure. Infusion through thecatheter/sheath would further drive the pressure within the filter.Thus, under higher flow rates, opening of the pores will facilitatehigher gas filtration capacity and allow for the filter to better meetthe increased demand for gas ventilation. The ability for decreased airresistance through the membrane under higher liquid pressures allows fora higher rate of passage of air through the membrane during higherliquid flow rate conditions. Therefore the air bubble filtrationcapacity of the device automatically adjusts with flow liquid rate and agreater volume rate of air bubbles may be captured and removed when mostneeded.

The outer wall consists of a stiff, densely-perforated (between 30-80%porosity) outer casing constructed using materials such as acrylates,ABS, polycarbonate, polyethylene, nylon, PVC or polypropylene, whichprotects the inner membrane from physical damage, permits transmissionof venting air (with minimal imposed resistance to air flow) andprevents overstraining of the inner membrane during high pressure flow.Porosity is defined by the ratio: (total open area on a surface)/(totalclosed and open surface area). The inner hydrophobic membrane is sizedto be smaller than that of the outer casing under neutral pressure (seeFIG. 1). This enables the membrane to stretch when fluid (see FIG. 2)pressures are higher than that of ambient, thus causing the pores toopen and decrease their resistance to air flow when fluid is enteringthe inlet of the filter.

The pores of this membrane may be diamond shaped, where their long axesare oriented in the axial direction of the filter (axial direction isthe principal direction of the fluid stream) (See FIG. 3). This shapefacilitates stress concentration points at the corners of the diamondpores, thus causing for more pronounced collapse of the pores undernegative gauge fluid pressures. (negative gauge pressures are thosewhere the pressure within the filter is below that external/outside ofthe filter), or under compressive membrane hoop stresses) to furtherdecrease permeability to air (see FIG. 4). Likewise, the shape allowsfor more pronounced opening of the pores under positive gauge fluidpressures (or tensile membrane hoop stresses) to further ease theresistance to air flow through the membrane (see FIG. 5).

In another embodiment, the filter is comprised of three components: (1)a microporous hydrophobic membrane, (2) a stiff, solid outer casing, and(3) one or more valves.

The microporous hydrophobic membrane forms the inner layer of the filterand serves as an obstruction to liquid but not to air. The pore size anddensity of the membrane are such to allow for sufficient rate transportof air volume across the filter membrane under anticipated pressuregradient ranges. A thicker membrane may be employed, than that describedfor the first variation (where thickness ranges between 0.050″ to0.200″), to allow for a more shape-stable membrane contour and greaterconsistency in flow patterns under varying fluid pressures.

With a thicker membrane, larger and/or greater density poreconfigurations (pore sizes ranging between 20-200 microns and 50-90%pore density) may be utilized to maintain the desired air filtrationcapacity.

The second element is the stiff, solid outer casing that protects theinner membrane from physical damage. This casing prevents over-strainingof the inner membrane during cases of high pressure flow.

The third element comprises one or more check-valves (one-way valves)that are incorporated into an un-perforated outer casing that isimpermeable to both gases and liquids. The valve(s) is/are aligned topermit fluids (gasses and liquids) from flowing from inside to outsidethe casing when the interior pressure is greater than exterior pressure.These valves permit exiting of gas that enters the space between themembrane and the outer casing, which has been originally vented fromwithin the inner membrane]. The valve is closed when the externalpressure exceeds or equals the internal pressure.

When air flows from the internal fluid medium and through the porousinner membrane, the resulting pressure created between the outer casingand inner membrane activates opening of the valve and venting of airfrom the outer casing (see FIG. 8). Under such conditions, where theinner fluid pressure may drop below that external (e.g. negativeinternal gage pressure), the valve shall close to prevent ambient airfrom entering through the outer casing and inner membrane (see FIG. 9).In the case of selection of a thin porous membrane (as described above),the inner hydrophobic membrane may be sized smaller than that of theouter casing under neutral pressure (see FIG. 1) to provide a means formodulation of the air venting rate based on the volumetric flow ratethrough the filter.

In addition to the pore shapes described above, the pores may be roundor oval in shape.

The hydrophobic membrane is joined at the inlet and outlet ends of thefilter to the outer casing by means of a compression fit between theouter casing and an inner stiff tubular member, i.e. the outer diameterof the inner stiff tubular member may be the same or slightly largerthan that of the outer casing at its inlet and outlet ends (see FIG. 6).The outer casing may include a circumferential groove and the innerstiff tubular member a matching notch to facilitate a stronger jointbetween the three said members. A gasket of ring clamp may also beemployed to provide a seal. An adhesive may also be applied within theinner layers of the compression fit to further improve the strength ofthe joint.

The gradual expansion of the filter diameter allows entering fluid tomaintain minimal flow separation relative to the inner surface, whilecausing a net decrease in the mean flow velocity within the expandedsection. In orientations where the filter is placed such that its axialaxis is near perpendicular to that of gravity, entering air/gas bubblesare pulled upward by resulting buoyancy forces and pressure gradients(see FIG. 7) across the hydrophobic membrane induced. When the axis ofthe filter is oriented approximately perpendicular to the axis ofgravity, buoyancy is a driver for gas bubbles to “rise” towards theinner surface of the membrane. The pressure gradient drives thepenetration of air/gas bubbles across the membrane. This pressuregradient exists independent of the orientation/position of the filterrelative to gravity.

The design of the filter is such that under reasonable volumetric flowrates, the advection speed of air bubbles in a decelerated flow withinthe filter is sufficiently slow that the buoyancy and pressure-gradientforces on the air bubble are able to carry it to the top of the filter.Once at the top of the filter, the bubble experiences decreased drag bythe blunt flow, as it has moved away from the main section of the fluidstream. By means of the imposed buoyancy, pressure gradient forces andthe physical obstruction presented by the nozzle end of the filter, theair bubble is held in a stable position for venting through thehydrophobic membrane. Buoyancy and pressure gradients act to drive gasbubbles towards the membrane, which is in a direction perpendicular tothe infusing flow. The acceleration and speed of the gas bubbles in the‘vertical’ direction (i.e. perpendicular to the filter axis) must besufficiently larger than the ‘horizontal’ speed of the bubbles so thatthe final termination of the trajectory of the bubbles is at themembrane. For example, in shorter length filters, where the ‘horizontal’speed of the air bubbles may be high, the buoyancy and pressuregradients would have to be large to ensure that the gas bubbles haveopportunity to make contact with the filter membrane for ventilation. In“blunt flow” the gas bubbles in contact with the membrane can beconsidered as a blunt object relative to liquid flow, which is imposinga drag on the bubbles. Thus the buoyancy is acting as a kinematic forceon the bubble.

To allow for flow stability and sufficiently decelerated flow within thefilter lumen, under worst-case high rate or turbulent flow conditions inthe inlet fluid line (where Reynolds number exceeds 60,000), the lengthof the filter (from the start of the diffuser to the end of the nozzle)must be at minimum of 8 times the difference between its largestdiameter and the entering fluid line diameter. In various embodimentsthe length of the filter may be 8, 9, 10, 12, 15 or 20 times thedifference between its largest diameter and the entering fluid linediameter.

The filter can be described as being constructed of a nozzle part (SeeFIG. 1) and a diffuser part (See FIG. 1). The nozzle and diffuser partsare joined together at a position between the center of the filter andabout ⅗^(th) to 9/10^(ths) of the way along the total length of thefilter (where measurement is taken from the inlet point of the filter)of the filter axis.

The filter is designed to be easily fitted or retro-fitted into anexisting line simply by cutting the line and inserting the filter bymeans of fluid-tight joints in the in-flow and out-flow sides. Standard,commercially available tube fittings may be employed to integrate thefilter into a line. The filter is designed to work with any type offluid to remove any type of gas bubbles.

In one exemplary embodiment the fluid is a biological fluid such assaline, blood, plasma, or any therapeutic solution, and the fluidcarrying line is an intravenous (IV) tube that carries liquids from areservoir to a patient.

In another embodiment, the filter may be used in a microfluidic devicefor performing polymerase chain reaction, chromatography, sequencing,chemical or physical analysis, or for growing crystals forcrystallography applications such as the devices described in USapplication Nos. 20020117517, 20050201901, 20060000513, and 20070138076.

Another embodiment and application of the present invention would be theuse of the filter in printers that dispense liquid ink, such as ink-jetprinters. Uninterrupted and consistent ink flow is critical in suchapplications and bubbles that block ink flow, for example in the printhead, are very problematical. The current filter addresses this problemby removing air bubbles from the liquid ink as it flows through adispensing line.

OBJECTS AND ADVANTAGES OF THE INVENTION

The invention provides an air filter capable of capturing and drawingair bubbles away from the main section of a fluid stream by means ofbuoyancy, air-specific pressure gradients and decelerating flow towardsa hydrophobic membrane for venting of the bubble out of the fluid line.The filter stores captured air bubbles in a fixed position away from thecentral core of the fluid stream, such that, under an anticipated rangeof volumetric flow rates, the venting process is decoupled from the rateof fluid entering the filter.

The filter may be constructed of a hydrophobic membrane of slow airventing properties but carrying a high water-intrusion pressurethreshold. Due to the fact that the cross-sectional profile of thefilter is large relative to the connecting fluid lines at the inlet andoutlet ends, the filter provides a highly energy efficient passivecomponent, as it presents little mechanical resistance to passing flowand therefore has little effect on fluid pressure. As the filtermaintains an open, non-constricting or obstructed lumen from its inletto outlet, the filter can be used in fluid lines, where solid objects,such as wires and tubes may be passed through. The axi-symmetric shapeof the air filter allows it to function in the same fashion regardlessof its circumferential orientation. Furthermore, the filter contourshape provides a degree of flexibility as to how the axial axis of thefilter is placed relative to that of gravity, while maintaining theintended functionality of the air filter.

The present invention provides the following advantages, amongst others.

1) It efficiently removes gas bubbles from a liquid-carrying line.2) It functions automatically with no active observation or manualoperation required.3) It is easy to use and simple to maintain.4) It is simple an inexpensive to manufacture.5) The invention functions without the need for power input.6) It captures and removes gas bubbles regardless of the flow rate ofthe fluid in the line. This has been demonstrated up to Re=4800, whichincorporates the workable & severe range of infusion rates withinmedical applications.7) The invention allows insertion of devices such as tubes and wires(catheters etc) through the device while in use without occlusion of thefluid flow path and without inhibition of its bubble-trapping function.8) The efficiency of the air venting and bubble-removing process isindependent of the fluid flow rate over a large range of Reynoldsconditions. The system has been experimentally validated up to Re.=4800.9) The device works to remove air bubbles in a wide range oforientations from horizontal to vertical.10) The device prevents intrusion of air during zero or negative gaugepressure conditions. 10) The low resistance design does not constrain orimpede fluid flow.11) The present invention does not use a split channel design, but usesa single channel design, thereby reducing overall resistance to flowwhen compared with the split channel design and allowing for insertionof wires and tubes.

Other Embodiments of the Invention

In addition to the embodiments described above, other embodiments ofdevices, systems, methods and kits for removing accumulated gas bubblesin a liquid-carrying line are encompassed by the present invention. Theinvention encompasses various equivalent embodiments that employmaterials and components that may differ from but be functionallyequivalent to the invention explicitly described.

The present invention may be employed in embodiments related to anysystem in which a liquid is flowed within a line, such as in industrialprocessing and manufacturing systems, and analytical and diagnosticsystems and in microfluidic systems, which are particularly susceptibleto interruption in fluid flow due to gas bubbles. In various exemplaryembodiments the air filter of the invention is fitted within a fluiddelivery line of a spectrometer, a sample dispenser or a microfluidicdevice dispensing volumes on liquid in the microliter or nanolitervolumes. The invention also encompasses a method of using the airfilters described by providing the air filter and placing it within afluid flow path within a liquid-carrying line. The invention alsoencompasses systems comprised of a device such as, for example, aspectrometer, sample dispenser a microfluidic device and an air filteras described. The invention further encompasses kits for fluidmanipulation that comprise at least a line adapted to contain a liquidand at least one air filter of the invention.

General Representations Concerning the Disclosure

The embodiments disclosed in this document are illustrative andexemplary and are not meant to limit the invention. Other embodimentscan be utilized and structural changes can be made without departingfrom the scope of the claims of the present invention. As used hereinand in the appended claims, the singular forms “a”, “an”, and “the”include plural reference unless the context clearly dictates otherwise.Thus, for example, a reference to “a part” includes a plurality of suchparts, and so forth.

In the present disclosure reference is made to particular features ofthe invention. It is to be understood that the disclosure of theinvention in this specification includes all appropriate combinations ofsuch particular features. For example, where a particular feature isdisclosed in the context of a particular embodiment or a particularclaim, that feature can also be used, to the extent appropriate, in thecontext of other particular embodiments and claims, and in the inventiongenerally.

The embodiments disclosed in this document are illustrative andexemplary and are not meant to limit the invention. Other embodimentscan be utilized and structural changes can be made without departingfrom the scope of the claims of the present invention. In the presentdisclosure, reference is made to particular features (including forexample components, ingredients, elements, devices, apparatus, systems,groups, ranges, method steps, test results, etc). It is to be understoodthat the disclosure of the invention in this specification includes allpossible combinations of such particular features.

As used herein and in the appended claims, the singular forms “a”, “an”,and “the” include plural reference unless the context clearly dictatesotherwise. Thus, for example, a reference to “a part” includes aplurality of such parts, and so forth.

The term “comprises” and grammatical equivalents thereof are used hereinto mean that, in addition to the features specifically identified, otherfeatures are optionally present. The term “at least” followed by anumber is used herein to denote the start of a range beginning with thatnumber (which may be a range having an upper limit or no upper limit,depending on the variable being defined). For example “at least 1” means1 or more than 1, and “at least 80%” means 80% or more than 80%. Theterm “at most” followed by a number is used herein to denote the end ofa range ending with that number (which may be a range having 1 or 0 asits lower limit or a range having no lower limit, depending upon thevariable being defined). For example, “at most 4” means 4 or less than4, and “at most 40%” means 40% or less than 40%. When, in thisspecification, a range is given as “(a first number) to (a secondnumber)” or “(a first number)-(a second number)”, this means a rangewhose lower limit is the first number and whose upper limit is thesecond number.

Where reference is made herein to a method comprising two or moredefined steps, the defined steps can be carried out in any order orsimultaneously (except where the context excludes that possibility), andthe method can optionally include one or more other steps which arecarried out before any of the defined steps, between two of the definedsteps, or after all the defined steps (except where the context excludesthat possibility). The numbers given herein should be construed with thelatitude appropriate to their context and expression; for example, eachnumber is subject to variation which depends on the accuracy with whichit can be measured by methods conventionally used by those skilled inthe art.

This specification incorporates by reference all documents referred toherein and all documents filed concurrently with this specification orfiled previously in connection with this application, including but notlimited to such documents which are open to public inspection with thisspecification.

1. A filter for capturing and removing accumulated gas bubbles presentin a liquid-carrying line, the filter adapted for integration into theliquid-carrying line, the filter comprising an expanded chamber havingan inlet end and an outlet end, wherein the maximum diameter of theexpanded chamber is greater than the diameter of the portion ofliquid-carrying line into which it is adapted to be integrated, andwherein the expanded chamber comprises a single inner wall and an outerwall constructed so as to form two concentric chambers having a liquidflow path through the axis of the inner chamber, and wherein the innerwall is, under conditions of use, permeable to gasses but impermeable toliquids.
 2. The filter of claim 1 wherein the shape of the expandedchamber is spherical or ovoid and wherein the shape of the expandedchamber is asymmetrical, having a generally narrower diameter close tothe inlet end and a generally broader diameter close to the outlet endsuch that in use, air bubbles present in the liquid carrying line areheld in a stable position for venting through the inner wall.
 3. Thefilter of claim 2 wherein the ratios of (inlet flow diameter):(maxluminal diameter):(total filter length) is between about 1:5.5:28 and1:9.5:54.
 4. The filter of claim 2 wherein the expanded chambercomprises a double-walled chamber having a first, inner wall and asecond, outer wall, resembling an inner bag that is contiguous with thefluid flow path through the line, and an outer bag that surrounds theinner bag, wherein the inner wall comprises a microporous membrane. 5.The filter of claim 4 wherein the microporous membrane comprises poresand wherein the average diameter of the pores is between 0.1-50 micronsunder zero hoop-stress.
 6. The filter of claim 4 wherein the microporousmembrane is comprised of a material selected from the group consistingof polytetrafluoroethylene, a glass composite, nylon, polyethersulfone,acrylic copolymer, vinylidene fluoride (VDF), tetrafluoroethylene,vinylidene fluoride, hexafluoropropylene, carbon black, and sulfur. 7.The filter of claim 4 wherein the microporous membrane becomesincreasingly gas permeable with increasing liquid pressures within theliquid flow path.
 8. The filter of claim 7 wherein, in use, the porestend to close under conditions of negative gauge pressure, inhibitinggas flow into the filter, but tend to open under conditions of positivegauge pressure, allowing gas flow out of the filter.
 9. The filter ofclaim 4 wherein the microporous membrane comprises pores that arediamond shaped.
 10. The filter of claim 4 wherein the outer wallcomprises a perforated, gas permeable material.
 11. The filter of claim4 wherein the outer wall comprises a material that is impermeable to gasand has valves integrated within it.
 12. The filter of claim 4 wherein,in use, the filter acts passively and automatically to trap and airbubbles present in the liquid flowing through the line.
 13. The filterof claim 4 wherein, in use, gas bubbles are captured and vented whileconcurrently using instruments passing through the liquid carrying line.14. The filter of claim 4 wherein, in use, with fluids having an inertiaof up to Re=4800, filtration efficacy is independent of flow rate. 15.The filter of claim 4 wherein, in use, accumulated gas bubbles presentin a liquid-carrying line are removed regardless of the orientation ofthe filter.
 16. The filter of claim 4 wherein the filter is adapted tobe inserted in-line into a conduit to provide a single-channel throughwhich liquid passes and gases are captured and vented.
 17. A systemcomprising the filter of claim 1 and a conduit, where the filter isplaced in-line with the conduit.
 18. The system of claim 17 wherein theconduit is part of a device selected from the group consisting of anintravenous line, an arterial line, a catheter, a sheath, a microfluidicdevice, a liquid chromatography device, a spectrophotometer, anucleotide sequencer, an analytical device, and an ink-jet printingdevice.
 19. The system of claim 17 wherein, in use, gases are capturedand vented while concurrently using instruments passing through theliquid carrying line
 20. The system of claim 17 specifically employing asingle channel design, and not a split channel design.